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Phase II Trial of Surgical Resection and Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) for Adrenocortical Carcinoma

Phase 2
18 Years
Open (Enrolling)
Adrenocortical Carcinoma, Peritoneal Carcinomatosis

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Trial Information

Phase II Trial of Surgical Resection and Heated Intraperitoneal Peritoneal Chemotherapy (HIPEC) for Adrenocortical Carcinoma


- Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of 1.5 to 2 per

million people per year and has a very poor prognosis with an overall 5-year mortality

rate of 75 - 90% and an average survival from the time of diagnosis of 14.5 months.

- The treatment of choice for a localized primary or recurrent tumor is surgical

resection. For unresectable metastatic or recurrent disease, mitotane,

aminoglutethimide, metapyrone, and ketoconazole are used.

- Cisplatin is one of the most effective chemotherapeutic agents for ACC. In the

Surgery Branch we have conducted Phase I and II trials using heated intraperitoneal

(IP) chemotherapy with cisplatin for primary peritoneal mesothelioma, low grade

appendiceal adenocarcinoma, ovarian malignancies, and high grade adenocarcinoma

of the gastrointestinal tract. Synergy has been demonstrated for cisplatin and


- The purpose of this trial is to determine if an aggressive surgical approach with

intraperitoneal administration of heated cisplatin when tumor volume is minimal, can

impact and improve on progression free survival.


- To determine IP progression free survival after optimal debulking and heated IP

chemotherapy with cisplatin in patients with IP spread of adrenocortical cancer

- Determine morbidity of this procedure in this patient population

- Determine the impact of surgery and HIPEC on QOL and hormone excess

- Examine patterns of recurrence (local versus systemic)

- Perform molecular analyses to try to discern if there are intrinsic differences between

tumors that recur widely throughout the peritoneal surface and those that metastasize

to other organs or are confined to a local recurrence.

- Determine overall survival after optimal debulking and heated IP chemotherapy with

cisplatin in patients with IP spread of adrenocortical cancer.


- Histologically proven ACC evalauable by CT imaging with the majority of disease

confined to the peritoneal cavity and surgically resectable to a residual size of less

than 1 cm or amenable to radiofrequency ablation in patients who are > 18 years of



- This is a classic phase 2 trial to determine efficacy of this therapeutic strategy in

ACC. Patients will undergo cytoreductive surgery to achieve a CCR of 0 or 1.

Patients who are successfully debulked will then undergo HIPEC with cisplatin.

Patients will be evaluated by associate investigators in coordination with the Principal

Investigator for eligibility. Due to its exploratory nature, up to 30 patients may be

enrolled to obtain 24 evaluable patients. (Patients must undergo successful debulking

and HIPEC to be considered evaluable.)

Inclusion Criteria


- Histologically proven ACC with the majority of disease confined to the peritoneal
cavity and resectable or amenable to radiofrequency ablation

- Disease evaluable by CT or PET imaging

- All disease should be deemed resectable with negative margins (NED) based on imaging
studies e.g.:

Hepatic metastases (unilateral or bilateral less than or equal to 5 lesions, less than or
equal to 15 cm total diameter)

Note: Hepatic lesions must be amenable to complete resection

Primary peritoneal metastases (small disease load less than or equal to P2 disease)
without massive ascites or intestinal obstruction

Including para-aortic lymph node metastases (stations 16 a1 and/or b2, see appendix D)

Lung metastases (less than or equal to 3 unilateral/bilateral, 9 cm total diameter)

Note: lung lesions must be amenable to complete resection

Patients who present with both hepatic and peritoneal metastases must have no evidence of
extensive para-aortic/retro-pancreatic lymph node metastases

Note: Patients with both pulmonary and hepatic metastases will be enrolled at the
discretion of the PI

Note: In situations where resection to Completeness of Cytoreduction Score (CC) 0 or 1 is
uncertain, patients may undergo diagnostic laparoscopy prior to enrollment to determine
feasibility of resection. (See Appendix E)

- Greater than or equal to 18 years of age

- Able to understand and sign the Informed Consent Document

- Clinical performance status of ECOG less than or equal to 2

- Life expectancy of greater than three months

- Patients of both genders must be willing to practice birth control during and for
four months after receiving chemotherapy

- Hematology:

Absolute neutrophil count greater than 1500/mm3 without the support of Filgrastim.

Platelet count greater than 75,000/mm3.

Hemoglobin greater than 8.0 g/dl.

- Chemistry:

Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine clearance
is greater than 60 mL/min/1.73 m2

serum AST and ALT within 5 times the upper limit of normal and a total serum bilirubin of
less than 3 times the upper limit of normal, both of which define the upper limit of grade
2 treatment related toxicities.

PT within 2 seconds of the upper limit of normal (INR less than or equal to 1.8)

- Recovered from any toxicity to grade 2 or less from all prior chemotherapy,
immunotherapy or radiotherapy and be at least 30 days past the date of their last
treatment with the exception of mitotane which may be continued.

- Able to understand their disease and the exploratory nature of combining surgery and
HIPEC for this histology.


- Concomitant medical problems that would place the patient at unacceptable risk for a
major surgical procedure.

- History of congestive heart failure and/or an LVEF less than 40%

Note: Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g.,
greater than 65yo, diabetes, history of hypertension, elevated LDL, first degree relative
with coronary artery disease) will undergo full cardiac evaluation and will not be
eligible if they demonstrate significant irreversible ischemia on stress thallium or an
ejection fraction less than 40%.

- Significant COPD or other chronic pulmonary restrictive disease with PFT's indicating an
FEV1 less than 50% or a DLCO less than 40% predicted for age

Note: Patients who have shortness of breath with minimal exertion or who are at risk for
pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will
not be eligible if their FEV1 is less than 50% of expected.

- Grade 2 or greater neuropathy

- Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the chemotherapy on the fetus or infant.

- Brain metastases or a history of brain metastases

- Childs B or C cirrhosis

- Evidence of severe portal hypertension by history, endoscopy, or radiologic studies

Note: Any diagnosis of portal hypertension or clinical stigmata of such including but not
limited to gastric or esophageal varices, umbilical vein varices or telangectasias.

- Weight less than 30 kg

- Active systemic infections, coagulation disorders or other major medical illnesses of
the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
arrhythmias, obstructive or restrictive pulmonary disease

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine intraperitoneal progression free survival after optimal debulking and heated intraperitoneal chemotherapy with cisplatin in patients with intraperitoneal spread of adrenocortical cancer.

Outcome Time Frame:

6 month intervals until peritoneal progression

Safety Issue:


Principal Investigator

Marybeth S Hughes, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

April 2013

Completion Date:

May 2019

Related Keywords:

  • Adrenocortical Carcinoma
  • Peritoneal Carcinomatosis
  • Adrenocortical Carcinoma
  • Surgical Resection
  • Heated Intraperitoneal Chemotherapy (HIPEC)
  • Carcinoma
  • Adrenocortical Carcinoma



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